Description du projet
Comprendre le rôle de la matrice extracellulaire dans les maladies cardiovasculaires
La matrice extracellulaire (MEC) est un vaste réseau de protéines et d’autres molécules qui soutiennent et organisent les cellules en tissus dans l’organisme. Il apparaît que la MEC est aussi un centre de communication qui transduit les stimuli mécaniques et facilite l’interaction entre les cellules. Financé par le Conseil européen de la recherche, le projet MATRICARD s’intéresse au rôle de la MEC dans les maladies cardiovasculaires. Pour ce faire, les chercheurs étudieront la composition de la MEC dans des conditions inflammatoires telles que l’athérosclérose et l’infarctus du myocarde, et la manière dont elle peut influencer la progression de la maladie. Les résultats du projet généreront de précieuses connaissances sur les mécanismes qui régulent la MEC dans des conditions de bonne santé et de maladie, tandis que l’identification de cibles thérapeutiques contribuera à la prévention des maladies cardiovasculaires.
Objectif
Cardiovascular diseases, as coronary artery disease (CAD) and its sequelae myocardial infarction (MI) and heart failure, represent the leading cause of morbidity and mortality in industrialized and developing countries. Atherosclerosis is the pathology causing CAD and MI; both are characterized by a sterile inflammation with a chronic and acute course of the disease, respectively. There is a plethora of cell types, as leukocytes, endothelial cells, vascular smooth muscle cells, platelets, fibroblasts, and cardiomyocytes, which play important roles in the initiation, propagation, and termination of the pathophysiological processes. Recent data from genetic studies found that genetic variation influencing extracellular matrix (ECM) proteins is associated with cardiovascular diseases. We found that such proteins which are secreted by one cell type influence phenotypes of other cell types via, e.g. silencing of inflammatory functions or modulation of ECM composition. The ECM hence not only represents a meshwork in which cells are organized but also a communication hub to transduce mechanical stimuli and cell-cell-interaction signals. Here, we aim to explore the ECM proteome in sterile inflammatory diseases as atherosclerosis and MI in an unprecedented depth. We aim to identify novel regulators which give insights into the underlying processes and we will study the molecular and cellular mechanisms modifying the course of the disease. This will lead to the identification of novel therapeutic targets which might reshape our understanding of how these diseases occur and how we can prevent them, and to the development of novel, individualized treatment strategies. Finally, we aim to translate our findings to humans to get first insights on whether these strategies can be adapted and used in clinical trials. MATRICARD will go beyond technical boundaries and lead to a deep knowledge of ECM-mediated cell-cell-communication and reveal its translational potential.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- social sciencessociologydemographymortality
- medical and health scienceshealth sciencesinflammatory diseases
- medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosis
- medical and health sciencesbasic medicinepathology
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
ERC - Support for frontier research (ERC)Institution d’accueil
80636 Munich
Allemagne